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ID 27758
file
creator
Miyano, Kanako
Tang, He-Bin
Nakamura, Yoki
Inoue, Atsuko
subject
DRG cells
Paclitaxel
PKC
sP
Vinorelbine
NDC
Medical sciences
abstract
Many patients suffer from serious adverse effects including respiratory distress and pulmonary edema during and after chemotherapy with paclitaxel or vinorelbine. These effects appear to be due to the activation of neurokinin-1 receptors. The present study investigated the influences of paclitaxel and vinorelbine on the substance P (sP) release from cultured dorsal root ganglion (DRG) cells using a radioimmunoassay. Both paclitaxel and vinorelbine evoked sP release in a dose- and time-dependent manner within 60 min at a concentration range of 0.1-10 mu M. The sP release levels induced by the two drugs were attenuated by pretreatment with the protein kinase Cs (PKCs) inhibitors (bisindolyimaieimide I and Go6976). Moreover, the paclitaxel- or vinorelbine-induced sP release was diminished in the absence of extracellular Ca2+ or the presence of LaCl3 (an extracellular Ca2+ influx blocker). A Ca2+ imaging assay further indicated that both paclitaxel and vinorelbine gradually increased the intracellular Ca2+ concentration, and these increases lasted for at least 15 min and were suppressed by Go6976. Paclitaxel caused the membrane translocation of only PKC beta within 10 min after stimulation, whereas vinorelbine induced the translocation of both PKC alpha and beta. The paclitaxel- and vinorelbine-induced sP release levels were separately inhibited by ruthenium red (a transient receptor potential (TRP) channel blocker) and gabapentin (an inhibitor of voltage-gated Ca2+ channels (VGCCs)). These findings suggest that paclitaxel and vinorelbine evoke the sP release from cultured DRG cells by the extracellular Ca2+ influx through TRP channels activated by PKC beta and VGCCs activated by both PKC alpha and beta, respectively.
journal title
Neuropharmacology
volume
Volume 57
issue
Issue 1
start page
25
end page
32
date of issued
2009
publisher
Pergamon-Elsevier Science Ltd
issn
0028-3908
ncid
publisher doi
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2009 Elsevier Ltd
relation url
department
Graduate School of Biomedical Science